Venous Thromboembolism (VTE) Prophylaxis in Pregnancy and The Puerperium

Department of Health
Maternity and Neonatal Clinical Guideline
Venous thromboembolism (VTE) prophylaxis

in pregnancy and the puerperium
Great state. Great opportunity.

Queensland Clinical Guideline: VTE prophylaxis in pregnancy and the puerperium
Document title: Venous thromboembolism (VTE) prophylaxis in pregnancy and the

puerperium
Publication date: February 2014
Document number: MN14.9-V5-R19
Document The document supplement is integral to and should be read in conjunction
supplement: with this guideline.
Amendments: Full version history is supplied in the document supplement.
Amendment date: Amendment October 2014. Full review of 2009 publication occurred in
February 2014.
Replaces document: MN14.9-V4-R19
Author: Queensland Clinical Guidelines
Audience: Health professionals in Queensland public and private maternity services
Review date: February 2019

Endorsed by: Queensland Clinical Guidelines Steering Committee
Statewide Maternity and Neonatal Clinical Network (Queensland)
Contact: Email: Guidelines@health.qld.gov.au
URL: www.health.qld.gov.au/qcg
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Flow Chart: Antenatal assessment and management for VTE prophylaxis
Antenatal VTE assessment and management

• Evidence correlating risk factors and the occurrence of VTE is limited
• Assess each woman individually for VTE risk. The flowchart does not replace clinical judgement
• Assess risk early in pregnancy, repeat if hospitalised and if there is a change in clinical circumstances
• Assess the risks associated with VTE prophylaxis (guideline section 1.4)
• Discuss options for VTE prophylaxis with the woman
• Document a plan of care
• Liaise with a team experienced in prophylactic assessment/management as required
• Refer to the full text of the guideline for detailed prophylaxis assessment and management
Antenatal therapeutic
Pre-pregnancy therapeutic anticoagulation
anticoagulation
High Risk Factors

• Single prior unprovoked VTE
• Single prior VTE pregnancy or COCP related High Risk
• Single prior VTE + thrombophilia • Discuss GCS
• Single prior VTE + family history of thrombophilia • #LMWH prophylaxis
Queensland Clinical Guideline: Venous thromboembolism (VTE) prophylaxis in pregnancy and the puerperium. Guideline No: MN14.9-V5-R19
• Prior recurrent VTE (>1) • Consider IPC if hospitalised
• Family history VTE (but no personal history VTE)
+ antithrombin deficiency
Hospitalised + ≥ 2 risk factors

Known Risk Factors or ≥ 3 risk factors
Socio-demographic Pregnancy related
• Age ≥ 35 years • Immobility (e.g. bed rest,
• BMI ≥ 30 kg/m2 long distance travel)
• Cigarette smoker • Preeclampsia/eclampsia
(>10/day) • Artificial reproductive
therapy Moderate Risk
Medical history • Gestational diabetes • Discuss GCS
• Systemic lupus • Consider IPC if hospitalised
• Multiparity (> 2)
erythematosus • Consider #LMWH prophylaxis
• Multiple pregnancy
• Cardiac or lung
disease • Intrauterine growth
restriction
• Sickle cell disease
• Hyperemesis/dehydration
• Gross varicose veins
• Current systemic infection
• Inflammatory (requiring antibiotics or
conditions 0 - 2 risk factors
hospitalisation)
• Nephrotic syndrome • Antepartum haemorrhage
• Cancer • Surgical procedure in
• Pre-existing diabetes pregnancy
• Ovarian
hyperstimulation
Lower Risk
VTE/Thrombophilias
• Single prior provoked VTE (not COCP related)
• Asymptomatic thrombophilia (inherited or acquired)
• Family history VTE
• Family history VTE (but no personal history VTE) + All Risk
thrombophilia (excluding antithrombin deficiency) • Clinical surveillance
• No personal or family history of VTE but significant • Encourage mobilisation
laboratory thrombophilia • Avoid dehydration
• Antiphospholipid antibodies
# Determine dose (standard, intermediate or therapeutic) based on individual assessment

Refer to full guideline - Section 5: Specific patient groups and Appendix A: Drug information.
Abbreviations: COCP: Combined oral contraceptive pill GCS: Graduated compression stockings HIT: Heparin induced thrombocytopenia
IPC: Intermittent pneumatic compression LMWH: Low molecular weight heparin ≥: Greater than or equal to >: Greater than

Flow Chart: Postnatal assessment and management for VTE prophylaxis
Postnatal VTE assessment and management

• Evidence correlating risk factors and the occurrence of VTE is limited
• Assess each woman individually for VTE risk. The flowchart does not replace clinical judgement
• Assess risk at birth and if there is a change in clinical circumstances
• Assess the risks associated with VTE prophylaxis (guideline section 1.4)
• Discuss options for VTE prophylaxis with the woman
• Document a plan of care
• Liaise with a team experienced in prophylactic assessment/management as required
• Refer to the full text of the guideline for detailed prophylaxis assessment and management
Postnatal therapeutic
Antenatal therapeutic anticoagulation
anticoagulation
High Risk
High Risk Factors • GCS
• Antenatal LMWH prophylaxis (refer to • #LMWH prophylaxis for
antenatal VTE prophylaxis flow chart) 6 weeks
• Any previous personal history of VTE (not • Consider IPC if
current pregnancy#) hospitalised
Known Risk Factors Emergency

Socio-demographic
CS in labour
Birth
• Age ≥ 35 years • Emergency CS in
• BMI ≥ 30 kg/m2 labour Moderate Risk
• Cigarette smoker • Elective CS • Discuss GCS
(>10/day) • Prolonged labour (> • #LMWH prophylaxis for
24 hrs) 5 days
Medical history • Operative vaginal birth • Consider IPC if
• Asymptomatic • Stillbirth hospitalised
thrombophilia • Preterm birth
(inherited or • Postpartum ≥ 3 risk
acquired) haemorrhage (> 1L) factors
• Family history VTE +
weak thrombophilia Postpartum
• Systemic lupus • Immobility (long
erythematosus distance travel,
• Cardiac or lung prolonged bed rest) Lower Risk
disease • Preeclampsia/ • Discuss GCS
• Sickle cell disease eclampsia 1-2 risk • Consider #LMWH
• Gross varicose veins • Gestational diabetes factors prophylaxis until
• Inflammatory • Infection discharge or fully
conditions • Any surgical mobile
• Nephrotic syndrome procedure
• Cancer
• Pre-existing diabetes
• Antiphospholipid All Risk
antibodies No risk • Clinical surveillance
factors • Early mobilisation
• Avoid dehydration
# Determine dose (standard, intermediate or therapeutic) based on individual assessment

Refer to full guideline - Section 5: Specific patient groups and Appendix A: Drug information.
Abbreviations: CS: Caesarean section GCS: Graduated compression stockings HIT: Heparin induced thrombocytopenia
IPC: Intermittent pneumatic compression LMWH: Low molecular weight heparin ≥: Greater than or equal to >: Greater than
Queensland Clinical Guideline: Venous thromboembolism (VTE) prophylaxis in pregnancy and the puerperium. Guideline No: MN14.9-V5-R19

Abbreviations
AOR Adjusted odds ratio
APCR Activated protein C resistance
APPT Activated partial thromboplastin time
bd Twice daily
BMI Body mass index
CI Confidence interval
COCP Combined oral contraceptive pill
CS Caesarean section
DVT Deep vein thrombosis
GCS Graduated compression stockings
GI Gastrointestinal
HIT Heparin induced thrombocytopenia
INR International normalised ratio
IPC Intermittent pneumatic compression
IV Intravenous
LMWH Low molecular weight heparin
PE Pulmonary embolism
PPH Postpartum haemorrhage
stat Immediately
Subcut subcutaneous
UFH Unfractionated heparin
VTE Venous thromboembolism
> Greater than
≥ Greater than or equal to
Terminology
2B
Term Definition
Family history of Family history is considered positive if one or more first degree relatives are
1,2
VTE affected.
When a woman has the autonomy and control to make decisions about her care after
a process of information exchange that involves providing her with sufficient, evidence-
Informed choice
based information about all options for her care, in the absence of coercion by any
3
party and without withholding information about any options.
When a woman consents to a recommendation about her care after a process of

information exchange that involves providing her with sufficient, evidence-based
Informed consent information about all the options for her care so that she can make a decision, in the
absence of coercion by any party, that reflects self-determination, autonomy and
3
control.
Local facilities may as required, differentiate the roles and responsibilities assigned in
this document to an ‘Obstetrician’ according to their specific practitioner group
Obstetrician
requirements; for example to General Practitioner Obstetricians, Specialist
Obstetricians, Consultants, Senior Registrars and Obstetric Fellows.
1
Provoked VTE VTE occurring where risk factors can be identified.
Recurrent VTE Two or more VTE.
Significant laboratory thrombophilia includes antithrombin deficiency, protein C and S
Significant
deficiency, homozygous factor V Leiden or multiple thrombophilic defects. All other
thrombophilia 1
thrombophilia are considered weak.
1
Unprovoked VTE VTE occurring where there are no identified risk factors.
Woman centred care includes the affordance of respect and dignity by supporting the
4 5
woman to be central and active in her own care through :
• Holistic care taking account of the woman’s physical, psychosocial, cultural,
emotional and spiritual needs
Woman centred
care • Focussing on the woman’s expectations, aspirations and needs, rather than the
institutional or professional needs
• Recognising the woman’s right to self-determination through choice, control and
continuity of care from a known or known caregivers
• Recognising the needs of the baby, the woman’s family and significant others
Table of Contents
1 Introduction ..................................................................................................................................... 7
1.1 Incidence................................................................................................................................ 7
1.2 Communication ...................................................................................................................... 7
1.3 Risk and benefit of VTE prophylaxis ...................................................................................... 7
1.4 Risks associated with VTE prophylaxis ................................................................................. 8
1.5 Signs and symptoms of VTE ................................................................................................. 9
1.6 Transfer of care ..................................................................................................................... 9
1.7 Clinical standards .................................................................................................................. 9
2 Risk assessment .......................................................................................................................... 10
2.1 High risk factors for VTE ...................................................................................................... 10
2.2 Known risk factors for VTE .................................................................................................. 11
2.3 Criteria for assessment of risk ............................................................................................. 12
2.4 Additional assessments ....................................................................................................... 12
3 Options for thromboprophylaxis ................................................................................................... 13
3.1 Other pharmaceutical agents............................................................................................... 14
4 Prophylactic management of VTE ................................................................................................ 15
4.1 Specific patient group management .................................................................................... 15
4.2 Antenatal prophylaxis .......................................................................................................... 15
4.3 Intrapartum prophylaxis ....................................................................................................... 15
4.4 Postnatal prophylaxis ........................................................................................................... 16
4.5 Neuraxial blockade .............................................................................................................. 17
5 Specific patient groups ................................................................................................................. 18
6 Discharge ..................................................................................................................................... 19
References .......................................................................................................................................... 20
Appendix A: Drug information .............................................................................................................. 22
Appendix B: Adjusted odds ratio (AOR) for risk of VTE ...................................................................... 23
Appendix C: Risk of VTE with Thrombophilia ...................................................................................... 24
Acknowledgements.............................................................................................................................. 25
List of Tables
Table 1. Risks associated with VTE prophylaxis ................................................................................... 8
Table 2. Signs and symptoms of VTE ................................................................................................... 9
Table 3. High risk factors for VTE ........................................................................................................ 10
Table 4. Known risk factors ................................................................................................................. 11
Table 5. Criteria for assessment of risk ............................................................................................... 12
Table 6. Additional risk assessment .................................................................................................... 12
Table 7. Options for thromboprophylaxis ............................................................................................. 13
Table 8. Other pharmaceutical agents ................................................................................................ 14
Table 9. Antenatal prophylaxis ............................................................................................................ 15
Table 10. Prophylaxis postpartum by assessment of risk ................................................................... 16
Table 11. Management of LMWH, UFH and neuraxial blockade ........................................................ 17
Table 12. Antenatal and postnatal management of specific patient groups ........................................ 18
Table 13. Preparation for discharge .................................................................................................... 19

1 Introduction
Pulmonary embolism (PE) and deep vein thrombosis (DVT) are the two components of a single
6,7
disease called venous thromboembolism (VTE). Pregnant women have an increased risk (4–5
1,7
fold ) of developing a VTE, in comparison to non-pregnant women due to hypercoagulability,
increased venous stasis, decreased venous outflow and compression of the inferior vena cava and
1
pelvic veins by the enlarging uterus.
1.1 Incidence
• Thromboembolism is a leading cause of maternal deaths in the developed world
8,9
1
o Second most common cause of direct maternal death in Australia
1
o Maternal mortality is reported to be 0.4–1.6 per 100,000 pregnancies
• The risk of VTE is greater postpartum than during the antenatal period
1,2,10
11
o 40–60% of antenatal VTE occur in the first trimester
• Rates of VTE are estimated at no more than 2 per 1000 pregnancies but vary
1,2
considerably
7 1
o 75–80% of events are caused by DVT and 20–25% by PE - of which 1 in 40 is fatal
2
o 43–60% of pregnancy related episodes of PE occur in the 4–6 weeks after birth
• DVT is more likely to occur in the left lower extremity
7
1.2 Communication
• Share and discuss information with the woman in a manner that enables informed choice
and consent and supports woman centred care [Refer to definition of terms]
• Discuss the woman’s preferences for management
2
• Provide the woman at increased risk of VTE, culturally appropriate information about
12
VTE , the risks of VTE prophylaxis and the symptoms suggestive of DVT and PE to
1
facilitate early recognition and management [Refer to Table 2. Signs and symptoms of
VTE]
1.3 Risk and benefit of VTE prophylaxis

Explain the risks and benefits of VTE prophylaxis as appropriate to the individual circumstances.
2
Including :
• Risk of VTE and consequences for the woman and her baby if no prophylaxis
• Relative effectiveness of treatment:
o Despite receiving low molecular weight heparin (LMWH), VTE occurred in 0.86% of
13
pregnancies(n=2777 pregnancies)
• Burden of prolonged compliance with treatment option
• Cautions and contraindications to prophylactic options
o Refer to Table 1. Risks associated with VTE prophylaxis
o Risk of significant bleeding
2
 Antepartum 0.43% (95% CI 0.22–0.75%) with LMWH
2
 Postpartum 0.94% (95% CI 0.61–1.37%) with LMWH
13
o With LMWH, the risk of (n=2777) :
 Allergic skin reactions (1.80%)
 Thrombocytopenia (0.11%)
 Osteoporotic fractures (0.04%)
 Heparin Induced Thrombocytopenia (HIT) (0%)
• The woman with very high risk conditions (mechanical heart valves, chronic
thromboembolic pulmonary hypertension, history of myocardial infarction, permanent
occlusion of a major vessel or a history of recurrent thrombosis while fully anticoagulated)
requires counselling and advice from a medical specialist as she is at increased risk of
14
maternal mortality

1.4 Risks associated with VTE prophylaxis

Table 1. Risks associated with VTE prophylaxis
Aspect Risk
• Active antenatal or postpartum bleeding (requiring at least two units of
blood/products to be transfused in 24 hours or PPH greater than 1 L)
• Chronic clinically significant and measurable bleeding over 48 hours
• Women at risk of major haemorrhage (e.g. placenta previa)
• Acquired or inherited bleeding disorders (e.g. acute liver failure,
haemophilia)
• Recent central nervous system bleeding
Patient-related • Intracranial or spinal lesion
risk factors for
15 • Abnormal blood coagulation
bleeding
• Thrombocytopenia
• Severe platelet dysfunction
• Active peptic ulcer or active ulcerative gastrointestinal disease
• Obstructive jaundice or cholestasis
• Recent major surgical procedure of high bleeding risk
• Concomitant use of medications that may affect the clotting process
• Regional axial or recent lumbar puncture
• *Contraindications to pharmacological therapy
o Known hypersensitivity
Cautions for o History of or current HIT
pharmacological o Creatinine clearance less than 30 mL/minute
15
prophylaxis • *Cautions to pharmacological therapy
o Renal impairment
o Hepatic impairment
• Recommend with caution where there is:
o Morbid obesity and correct fitting stocking cannot be achieved
o Inflammatory conditions of the lower legs
o Severe peripheral neuropathy
Mechanical
15 o Severe oedema of the legs
prophylaxis
o Diabetic neuropathy
o Severe lower limb deformity
• Intermittent pneumatic compression device (IPC) can exacerbate ischaemic
disease
*Consult an Australian pharmacopeia for complete drug information

1.5 Signs and symptoms of VTE

Table 2. Signs and symptoms of VTE
Type Clinical presentation

• Dyspnoea (most common symptom of PE)
• Palpitations
• Chest pain
• Haemoptysis
Pulmonary
11 • Hypoxia/Cyanosis
embolism
• Tachycardia
• Tachypnoea
• Hypotension
• Collapse
• DVT in pregnancy is often proximal and may not present with usual
16
features of distal DVT
• Unilateral leg pain
•
7,9
Deep Vein Swelling in an extremity
•
7
Thrombosis Increase in calf/thigh circumference
•
11
Increased temperature
•
11
Prominent superficial veins
•
11
Pitting oedema
1.6 Transfer of care

• Provide care in accordance with local service capabilities
17
• Consult with, refer or transfer care to higher level services as appropriate

18
• Document processes for referral and transfer appropriate to the local facility
1.7 Clinical standards

• Educate clinicians about VTE risk assessment
• Document VTE risk assessment of the pregnant woman in the health record
o Develop a written plan of care to manage identified risks
o Document completion of the inpatient risk assessment on the National Inpatient
Medication Chart
• Measure and document observations consistent with the clinical situation and at a
19
minimum, the Australian Commission on Safety and Quality in Health Care requirements
• Consider use of Queensland Maternity Early Warning Tools to detect deterioration of
8
pregnant patients
• Use standard administration forms for prophylactic and therapeutic medications (e.g.
20,21
Heparin intravenous infusion order and administration form)
o For Dalteparin, write the brand name in addition to the generic name to reduce
22
ambiguity

2 Risk assessment
Failure to recognise and/or treat personal or pregnancy specific risk factors has been identified as a
1,10
significant contributing factor to maternal mortality and morbidity arising from thrombosis.
However, there is limited high level evidence from randomised trials or among evidence
23
based/consensus guidelines about which women require thromboprophylaxis during pregnancy and
1,9,15
postpartum.
• Assess all women for VTE risk factors in early pregnancy or before conception
1,10
• Repeat the assessment when there is a change in risk status and following birth
11
o Ask about VTE symptoms

o Commencing prophylaxis at times of additional VTE risk is clinically important and
1
appropriate
• Assess the woman’s risk of bleeding and/or contraindications to pharmacological or
15,24
mechanical prophylaxis before offering VTE prophylaxis [refer to Table 1]
• Formulate an overall risk assessment with consideration of risk of thromboprophylaxis
15
against the benefits [Refer to Section 1.2]
• Refer to Section 5 Specific patient group for management if identified risk factor(s) include
any of the following:
o Significant personal history of VTE
o Thrombophilia
o Antiphospholipid syndrome
o Pre-pregnancy anticoagulation
2.1 High risk factors for VTE

The strongest personal risk factor for VTE in pregnancy is a history of thrombosis - 15–25% of VTE in
pregnancy are recurrent events, followed by thrombophilia - present in 20–50% of women who
14
experience VTE during pregnancy and postpartum.
Table 3. High risk factors for VTE
Period High risk factors

• Single prior unprovoked VTE
• Single prior VTE pregnancy or combined oral contraceptive pill (COCP)
related
• Single prior VTE and thrombophilia
Antenatal
• Single prior VTE and family history of thrombophilia
• Prior recurrent VTE (>1)
• Family history VTE (but no personal history VTE) and antithrombin
deficiency
• Antenatal LMWH
Postnatal
• Any personal history of VTE

2.2 Known risk factors for VTE

The evidence correlating risk factors and the occurrence of VTE is imprecise with wide and
1
sometimes contradictory estimates of risk [Refer to Appendix B]. The presence of multiple risk
1,10,15
factors may have additive or synergistic effects but the combinations with the greatest risk are
unknown. It is unclear from the evidence whether particular risk factors are more likely to be
associated with antenatal or postnatal VTE (or both).
Table 4. Known risk factors
Risk factors
•
25-29
Age (greater than 35 years)
Socio-
• BMI ≥ 30 kg/m
2,26,27,30-33
demographic
•
26,28,30,31
Cigarette smoker (>10/day)
•
26,29,33
Single previous VTE with no family history VTE or thrombophilia
•
26
Thrombophilia and no previous VTE
•
1
Family history VTE
•
1
Antiphospholipid syndrome
•
10
Thrombophilia (inherited or acquired)
•
26
Systemic lupus erythematosus
•
26,31
Cardiac or lung disease
Medical history
•
26
Sickle cell disease
•
10
Ovarian hyperstimulation syndrome
•
31,32
Gross varicose veins
•
24,32
Inflammatory conditions
•
32
Nephrotic syndrome
•
24
Cancer
•
32
Pre-existing diabetes
•
30
Immobility (e.g. bed rest, long distance travel)
•
25,28-30,34
Preeclampsia/eclampsia
•
25,30,34
Artificial reproductive therapy (ART)
•
25,30
Gestational diabetes
•
27,28,31 29
Multiparity (greater than 2 or 3 )
Pregnancy
•
25,26,28,30,34
Multiple pregnancy
related
•
30
Intrauterine growth restriction
•
26
Hyperemesis/dehydration
•
32
Current systemic infection (requiring antibiotics or hospitalisation)
•
25,26
Antepartum haemorrhage
•
24
Surgical procedure in pregnancy
•
10
Prolonged labour (greater than 24 hours)
•
26,28,29,31-34 25,30 25
Caesarean section (emergency and elective )
•
10
Operative vaginal birth
•
32
Stillbirth
Birth/
•
31,32,35
Preterm birth
Postpartum
•
26,30,32,35
PPH (> 1L)
•
26
Transfusion
•
24
Any surgical procedure in the puerperium
•
26,30
Postpartum infection

2.3 Criteria for assessment of risk

Consider the potential for additive effects of multiple risk factors. Refer to Appendix B Adjusted odds
ratio (AOR) for risk of VTE.
Table 5. Criteria for assessment of risk
Risk assessment Antenatal criteria Postnatal criteria

• All pregnant women are at • All postnatal women are at
All risk
increased risk for VTE increased risk for VTE
Therapeutic • Pre-pregnancy therapeutic • Antenatal therapeutic
anticoagulation anticoagulation anticoagulation
• One or more antenatal high risk • One or more postnatal high risk
High risk
factors factors
• 3 or more known risk factors • Emergency caesarean birth in
Moderate risk • If hospitalised, 2 or more known labour
risk factors • 3 or more known risk factors
Lower risk • 0-2 antenatal known risk factors • 1-2 postnatal known risk factors
2.4 Additional assessments

Table 6. Additional risk assessment
Aspect Consideration
• A positive family history of VTE has been shown to increase the risk of VTE
1
two-fold
• Refer the woman with a positive personal or family history of VTE to an
obstetrician or physician experienced in VTE prophylaxis management
• All women with previous VTE require a full thrombophilia screen
10
including :
o *Activated protein C resistance (APCR)
o Factor V Leiden mutation will be done if APCR is detected
o Prothrombin gene mutation
o *Antithrombin III deficiency
Previous VTE o *Protein C deficiency
o *Protein S deficiency
o Antiphospholipid antibodies:
 Lupus anticoagulant
 *Anticardiolipin antibodies
 Beta 2 Glycoprotein 1 (B2GP1)
Note: High risk thrombophilia include: Homozygous Factor V Leiden mutation,

Antithrombin III deficiency and the presence of multiple thrombophilia are
1
associated with a higher risk for VTE
*Test in non- pregnant state as range affected by pregnancy
• Liaise with an obstetrician and physician experienced in prophylactic
management of VTE where the woman has a history of:
o Cerebral haemorrhage
o Gastrointestinal haemorrhage
Pre-existing o HIT/Thrombocytopenia
medical o Renal insufficiency
conditions
• Ensure a multidisciplinary approach to care
• Thromboprophylaxis may need to be individualised
• Ensure referral to anaesthetics team to discuss management plan
peripartum

3 Options for thromboprophylaxis

Table 7. Options for thromboprophylaxis
Method Considerations
• Encourage and educate the pregnant woman about the importance of:
Non-
pharmacological o Mobilisation
o Avoidance of dehydration
• There is limited high quality evidence about the use of graduated elastic
compression stockings (GCS) during pregnancy and the puerperium
• GCS are effective in diminishing the risk of DVT in non-pregnant
hospitalised patients when used alone, with increased benefit when used in
36
conjunction with another method of prophylaxis
• There is limited high quality evidence about the effectiveness of knee
37
length versus thigh length GCS
• GCS
Mechanical o Patient compliance is essential – encourage to wear as much as
possible
o Contraindicated in critical limb ischemia
o Should be measured and fitted for each woman
o A health professional trained in garment sizing and application can
assist with GCS selection and fitting
o Check skin integrity regularly
• Intermittent pneumatic compression device (IPC) in combination with other
prophylactic modalities has been shown to reduce the incidence of DVT in
38
high-risk non-pregnant patients
• Low molecular weight heparin (LMWH)
2
o Agent of choice for antenatal thromboprophylaxis
2,9
o Does not cross placenta
2
o No evidence of teratogenicity or increased risk of fetal bleeding
o Associated with fewer bleeding episodes compared with
13
Unfractionated Heparin (UFH)
2
o Risk of HIT lower with LMWH than with UFH
2
o Risk of osteoporosis lower with LMWH than UFH
o Refer to Department of Health: Anticoagulation and prophylaxis using
Pharmacological LMWH in adult inpatients
39
• Unfractionated heparin
• Warfarin:
o Contraindicated antenatally for thromboprophylaxis
o Consider postnatal only for prolonged thromboprophylaxis or treatment
o If warfarin used pre-pregnancy recommence postpartum
o Refer to Appendix A for pharmacological information
• Note: LMWH, UFH and Warfarin are safe for breastfeeding mothers
2

3.1 Other pharmaceutical agents

Table 8. Other pharmaceutical agents
Agents Considerations
• There is limited information about the use of newer pharmacological agents
(e.g. Rivaroxaban) during pregnancy and their safety while
16,40
breastfeeding
• The American College of Chest Physicians recommend :
2
o Pregnant women: limit the use of Fondaparinux to those with severe

allergic reactions to Heparin who cannot receive Danaparoid
o Pregnant women: avoid the use of oral direct thrombin (e.g. Dabigatran
Newer agents
and Factor-Xa inhibitors (e.g. Rivaroxaban, Apixaban)
o Breastfeeding women: use alternative anticoagulants rather than
Fondaparinux and Factor Xa inhibitors (e.g. Rivaroxaban)
• Not recommended in conjunction with neuraxial blockade
41
• Discuss newer agents with a team experienced in their use

• Refer to Department of Health: Guideline for managing patients on a factor
42
Xa inhibitor - Apixaban (Eliquis®) or Rivaroxaban (Xarelto®)
• There are no controlled trials on the use of aspirin for thromboprophylaxis
10
in pregnancy
• The American College of Physicians recommend against the use of aspirin
2
for VTE in any patient group
Aspirin • No adverse fetal outcomes were reported in a meta-analysis of large
randomised controlled trials of low-dose aspirin for the prevention of
43
preeclampsia in pregnancy
• There is insufficient evidence to recommend routine use of aspirin for
thromboprophylaxis in the antenatal and postnatal period at this stage

4 Prophylactic management of VTE

Regardless of risk for VTE, minimise immobilisation and dehydration.
• Routine laboratory thrombophilia screening of pregnant women is not recommended
1,2
• If anticoagulation is required peripartum a multidisciplinary team approach is essential

o Develop a plan for the peripartum management of anticoagulation (prophylactic or
therapeutic)
• Determine dose of prophylaxis (standard, intermediate or therapeutic) based on the
assessment of an individual’s risk for VTE
4.1 Specific patient group management

If identified risk factor(s) include any of the following, refer to Section 5 for specific patient group
antenatal and postnatal management:
o Significant personal history of VTE
o Thrombophilia
o Antiphospholipid syndrome
o Long-term therapeutic coagulation
4.2 Antenatal prophylaxis

UFH may be substituted for LMWH at the discretion of the obstetrician/physician in anticipation of
birth.
Table 9. Antenatal prophylaxis
Risk assessment Antenatal prophylaxis

• Clinical surveillance
All risk
(all antenatal women)
• Encourage mobilisation
• Recommend GCS
• Consider IPC if hospitalised
High risk
•
#
Recommend prophylaxis with LMWH
• Liaise with a treating team experienced in prophylactic management
• Discuss GCS
• Consider IPC if hospitalised
•
#
Moderate risk Consider prophylaxis with LMWH
• Liaise with a treating team experienced in prophylactic management as
required
Lower risk • As for all risk women
#
Determine dose (standard, intermediate or therapeutic) based on individual assessment
4.3 Intrapartum prophylaxis

For the woman receiving intermediate or high risk antenatal thromboprophylaxis:
• Document a plan of care that considers individual risk factors and clinical circumstances
o Discuss the plan with the woman prior to labour and birth
• Liaise with a multidisciplinary team regarding:
o Timing of anticoagulation cessation prior to established labour/planned birth
o Timing for recommencement of thromboprophylaxis following birth
• Consider precautions related to neuraxial blockade [Refer to Section 4.5]

4.4 Postnatal prophylaxis

• The risk of VTE is greater after caesarean section than after vaginal birth however, the
woman with multiple risk factors giving birth vaginally may still require specific VTE
prophylaxis
• Postpartum prophylaxis should begin as soon as possible after birth
15
• UFH may be substituted for LMWH at the obstetrician/physician’s discretion [refer to

Appendix A]
• Consider precautions regarding neuraxial blockade management [Refer to Section 4.5]
Table 10. Prophylaxis postpartum by assessment of risk
Risk Assessment Clinical care

• Clinical surveillance
All risk
(all postnatal women)
• Early mobilisation
• GCS until mobilising
• Consider IPC
•
#
High risk Recommend prophylaxis with LMWH for 6 weeks
• Refer to Section 5 Specific patient groups
• Liaise with a treating team experienced in prophylactic management
• Discuss GCS (until mobilising)
•
#
Recommend prophylaxis with LMWH:
Moderate risk 10,15
o Commence within 4 hours after giving birth
o Continue until day 5 postpartum
o If not fully mobile at day 5, then continue prophylaxis until fully mobile
• Discuss GCS
• Consider prophylaxis with LMWH
#
10,15
Lower risk o Commence within 4 hours after giving birth
o Continue until discharge or until fully mobile
• If hospitalised more than 5 days, medical staff review required regarding
continuation/cessation of prophylaxis
#
Determine dose (standard, intermediate or therapeutic) based on individual assessment

4.5 Neuraxial blockade

Table 11. Management of LMWH, UFH and neuraxial blockade
Aspect Clinical care

• Safety of a neuraxial blockade in patients receiving anticoagulation
depends on:
o Anticoagulant used
o Timing of insertion
o Whether catheter is left in situ
Context o Timing of removal
• Spinal haematoma, the most serious complication, is a clinical emergency
1
o Tends to occur at either insertion or removal of a neuraxial catheter

• Consider risk and benefit relative to the clinical circumstances
o Provide information to the woman to support informed decision making
• Formulate a written plan of care
• Refer to and discuss with the anaesthetic team
Plan care
• Monitor for evidence of neuraxial haematoma for 24 hours after insertion or
removal of a neuraxial block
• Wait at least 12 hours after LMWH dose before performance of neuraxial
LMWH
block or removal of catheter
prophylactic
dose
41 • Wait at least 4 hours following neuraxial blockade or neuraxial catheter
removal before giving subsequent LMWH dose
• Avoid therapeutic dosing with catheter in situ if possible
LMWH • Wait at least 24 hours after the last therapeutic dose LMWH before
therapeutic performing neuraxial blockade or removing catheter
41
dose • Wait at least 4 hours after performing neuraxial blockade or removing
catheter before giving subsequent LMWH dose
• Wait at least 4 hours after last dose of UFH (doses ≤ 10,000 U) before
UFH
performing neuraxial blockade or removing catheter
prophylactic
41 • Wait at least 1 hour after performing neuraxial blockade or removing a
dose
catheter before giving subsequent UFH dose
• Stop intravenous UFH at least 4 hours prior to performing neuraxial
blockade or removing catheter
UFH
• Document normal activated partial thromboplastin (APTT) (3–4 hours after
therapeutic
41 stopping infusion)
dose
• Wait at least 4 hours after performing neuraxial blockade or removing
catheter before giving subsequent UFH dose
• There is limited data on the safety of newer drugs (e.g. Fondaparinux,
Newer agents Rivaroxaban) and they are therefore not currently recommended in
41
conjunction with neuraxial blockade

5 Specific patient groups

There is limited evidence to determine best practice. Each woman should be assessed on an
individual basis and referred to a physician experienced in this area. Where pharmacological
prophylaxis is indicated, also consider mechanical methods of prophylaxis (e.g. GCS, IPC) [refer to
Table 7. Options for thromboprophylaxis] and Appendix A: Drug Information for dosing.
Table 12. Antenatal and postnatal management of specific patient groups
Liaise with a team experienced in this area regarding prophylaxis management

Patient group Antenatal management Postpartum management
• Single previous unprovoked VTE • Prophylaxis recommended • Prophylaxis for 6 weeks
• Single previous pregnancy (standard dose) (standard dose)
associated VTE
• Previous recurrent VTE
• Single previous VTE and
thrombophilia
• Single previous VTE associated
with combined oral contraceptive
pill (COCP)
• Single previous provoked VTE • Clinical surveillance unless • Prophylaxis for 6 weeks
(excluding those associated with other risk factors (standard dose)
COCP)
• Any previous VTE and • These women may be on • Therapeutic anticoagulation
antithrombin deficiency long term anticoagulants for 6 weeks or longer
• Recurrent unprovoked VTE • Therapeutic anticoagulation
required throughout
pregnancy
• Long term anticoagulation any • Therapeutic anticoagulation • Return to pre-pregnancy
indication • Monitor in high risk clinic therapeutic anticoagulation
• Administer therapeutic
intravenous UFH or LMWH
until therapeutic
anticoagulation achieved
• Refer to usual treating
healthcare team at discharge
• Antenatal VTE current • Therapeutic anticoagulation • Management depends on
pregnancy • Discuss duration with an timing of antenatal VTE
experienced team • Discuss with an experienced
team
• Positive family history VTE but • Consider intermediate dose • Therapeutic anticoagulation
no personal history VTE, with prophylaxis or therapeutic for 6 weeks
antithrombin deficiency anticoagulation
• Positive family history VTE but • Prophylaxis favoured • Prophylaxis for 6 weeks
no personal history VTE with especially if other risk (standard dose)
significant laboratory factors (standard dose)
thrombophilia (excluding
antithrombin deficiency)
• No personal or family history of • Clinical surveillance • Consider prophylaxis for 6
VTE but significant laboratory • Consider prophylaxis weeks (standard dose)
thrombophilia (standard dose)
• Positive family history VTE but • Clinical surveillance unless • Consider prophylaxis for 6
no personal history VTE and/or other risk factors weeks especially if other risk
weak laboratory thrombophilia factors (standard dose)
• Antiphospholipid syndrome and • Prophylaxis required • Prophylaxis for 6 weeks
previous VTE • Discuss dose with an • Discuss dose with an
experienced team experienced team
• Antiphospholipid antibodies and • Clinical surveillance • Prophylaxis 5-7 days
no previous VTE postpartum
Adapted from: McLintock C ,Brighton T ,Chunilal S ,Dekker G ,McDonnell N ,McRae S, et al. Recommendations for the
prevention of pregnancy-associated venous thromboembolism. Aust N Z J Obstet Gynaecol. 2012; 52(1):3-13

6 Discharge
Table 13. Preparation for discharge
Aspect Considerations
• Offer women and their families verbal and written information on :
12
o Signs and symptoms of VTE [Refer to Table 2]

o How to reduce the risk of VTE (e.g. keep well hydrated and mobilise
frequently)
o Risks and possible consequences of VTE
Discharge o Importance of VTE prophylaxis [Refer to Section 1.2]
information
24 o Correct use/application and duration of recommended treatment
including onset of action, monitoring requirements, and side effects of
recommended treatment
o The importance of seeking help and who to contact if concerned
o Discuss future anti-coagulation needs for subsequent pregnancies
o The risk of VTE with prolonged periods of immobility (e.g. long
distance travel)
• Complete a discharge summary/referral to the women’s local medical
Follow-up
officer and if appropriate to the treating specialist

References
1. McLintock C, Brighton T, Chunilal S, Dekker G, McDonnell N, McRae S, et al. Recommendations for the prevention of
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Appendix A: Drug information

The choice of drug is dependent on availability, clinical circumstances, patient preferences, and clinician familiarity.
Note: Although there is limited data on the dosing of LMWH in pregnant women, obese women and women with renal impairment, the current doses are determined
on standard practice worldwide. Liaise with an experienced team and/or pharmacist regarding LMWH dosing and monitoring for women greater than 100 kg (actual
weight) or with renal impairment.
Determine dose (standard, intermediate or therapeutic) based on assessment of an individual’s risk for VTE. Refer to Section 5: Specific patient groups
Caution: refer to Australian Medicine Handbook for complete drug information

Dose Prophylactic STANDARD dose Prophylactic INTERMEDIATE dose THERAPEUTIC dose
for weight 50-100 kg
Liaise with experienced team if actual weight
less than 50 kg or more than 100 kg
Less than 50 kg: 2500 units subcut once daily

Dalteparin
50–100 kg: 5000 units subcut once daily 5000 units subcut twice daily 100 units/kg twice daily
(Fragmin)
Greater than 100 kg: 7500 units subcut once daily
Antenatal: 1mg/kg subcut twice daily

Less than 50 kg: 20 mg subcut once daily Postnatal: 1.5 mg/kg subcut daily
Enoxaparin
50–100 kg: 40 mg subcut once daily 40 mg subcut twice daily • Check renal function prior to initiating
(Clexane)
Greater than 100 kg: 60–80 mg subcut once daily • If weight greater than 100 kg liaise with
experienced physician regarding dose
Loading Dose: 80 units/kg IV stat
Less than 50 kg: Consider reduced dose Infusion: 18 units/kg/hour IV infusion
Sodium
50-100 kg: 5000 units subcut twice daily 7500 units subcut twice daily • Monitor APTT as per Queensland Health’s
Heparin
More than 100 kg: 7500 units subcut twice daily Heparin Intravenous Infusion Order and
Administration - Adult form
Variable oral dose
Warfarin
Do not use Do not use • Aim for INR 2-3 unless specified otherwise
(postnatal) • Refer to Queensland Health’s guidelines for
anticoagulation using Warfarin*
*Queensland Health, Health Services Support Agency http://qheps.health.qld.gov.au/hssa/home.htm
Adapted from: Royal College of Obstetricians and Gynaecologists. Reducing the risk of thrombosis and embolism during pregnancy and the puerperium. Green-top Guideline No.37a. 2009.

Appendix B: Adjusted odds ratio (AOR) for risk of VTE

in pregnant and postpartum women compared with pregnant and postpartum women without these
risk factors
Risk Factor AOR 95%CI Comment

Previous VTE 24.8 17.1–36 n=603
Age >35 1.3 1.0–1.7 pn=256
1.4 1.0–2.0 n=143 an PE
2
BMI >30 mg/kg 2.65 1.09–6.45 n=129
5.3 2.1–13.5
4.4 3.4–5.7
1.7 1.2–2.4 pn=256
2
BMI >25 mg/kg 1.8 1.3–2.4 an=268
2.4 1.7–3.3 pn=291
1.7 1.2–2.4 pn=256
Parity 1 4.03 1.6–9.84 n=143 an PE
Parity 2 1.5 1.1–1.9 n=603
Parity 3 2.4 1.8–3.1 n=603
Smoking 2.1 1.3–3.4 an=268
Smoking 10–30/day 3.4 2.0–5.5 pn=291
1.4 1.1–1.9 n=603
2.5 1.3–4.7 n=90
Current smoker 2.7 1.5–4.9 n=129
Sickle cell 6.7 4.4–10.1
2.5 1.5–4.1 DVT
1.7 0.9–3.1 PE
Heart disease 7.1 6.2–8.3
5.4 2.6–11.3 pn=256
SLE 8.7 5.8–13
Anaemia 2.6 2.2–2.9
Varicose veins 2.4 1.04–5.4
Immobility 7.7 3.2–19 an
10.8 4.0–28.8 pn
Preeclampsia 2.9 2.1–3.9
3.1 1.8–5.3
Preeclampsia + fetal growth restriction 5.8 2.1–16
Hyperemesis 2.5 2–3.2
Assisted reproductive technology 4.3 2.0–9.4 an
Twins 2.6 1.1–6.2 an
Multiple pregnancy 4.2 1.8–9.7 n=603
Preterm delivery <36 weeks 2.4 1.6–3.5 an=109
Antepartum haemorrhage 2.3 1.8–2.8 pn=256
Emergency caesarean section 2.7 1.8–4.1
Any caesarean section 3.6 3.0–4.3 pn=256
Postpartum haemorrhage >1 L 4.1 2.3–7.3
Postpartum haemorrhage + surgery 12 3.9–36.9
Obstetric haemorrhage 9 1.1–71
Postpartum infection 4.1 2.9–5.7
Postpartum infection + caesarean section 6.2 2.4-16.2
Transfusion 7.6 6.2–9.4
an=antenatal; pn=postnatal; n=number of cases in case-control study;
Source: Royal College of Obstetricians and Gynaecologists. Reducing the risk of thrombosis and embolism during pregnancy
and the puerperium. Green-top Guideline No.37a. 2009.

Appendix C: Risk of VTE with Thrombophilia
Adjusted odds ratio for risk of VTE in pregnancy and/or postpartum with different
thrombophilia
Risk of VTE
Thrombophilia
Odds Ratio Odds Ratio 95% CI
Antithrombin deficiency 10–unknown 4.7 1.3–17.0
Protein C deficiency 2–unknown 4.8 2.2–10.6
Protein S deficiency – 3.2 1.5–6.9
Factor V Leiden (heterozygous) 5–7 8.3 5.4–12.7
Prothrombin G20210A (heterozygous) 3–10 6.8 2.5–18.8
Factor V Leiden (homozygous) 10–41 34.4 9.9–120.1
Prothrombin G20210A (homozygous) – 26.4 1.2–559.2
Compound heterozygote (Factor V Leiden and prothrombin
9–107 – –
G20210A)
Estimated absolute risk of VTE with different thrombophilic defects in women with one or
more symptomatic first degree relatives
Thrombophilic defect Pregnancy Antenatal Postpartum
%/pregnancy 95% CI %/pregnancy 95% CI %/pregnancy 95% CI
Antithrombin, Protein C, Protein S
4.1 1.7–8.3 1.2 0.3–4.2 3.0 1.3–6.7
deficiency
15–50
Antithrombin deficiency type 1* – 0–40 – 11–28 –
(range)
Factor V Leiden (heterozygous) 2.1 0.7–4.9 0.4 0.1–2.4 1.7 0.7–4.3
Prothrombin G20210A
2.3 0.8–5.3 0.5 0.1–2.6 1.9 0.7–4.7
(heterozygous)
Factor V Leiden (homozygous) or
Compound heterozygote (Factor 1.8–15.8
– 0–5 – 1–10 –
V Leiden and prothrombin (range)
G20210A)
*Population-based not family study

Acknowledgements
Queensland Clinical Guidelines gratefully acknowledges the contribution of Queensland clinicians
and other stakeholders who participated throughout the guideline development process particularly:
Working Party Clinical Lead

Dr Karin Lust, Obstetric Physician, Royal Brisbane and Women’s Hospital, Brisbane
Working Party Members

Ms Noor Aladhami, Pharmacist, Royal Brisbane and Women’s Hospital
Mrs Anne Bousfield, Midwifery Unit Manager, Roma Hospital
Dr Stephen Elgey, Staff Specialist, Obstetrics and Gynaecology, Logan Hospital
Dr Hasthika Ellepola, Staff Specialist, Obstetrics and Gynaecology, Logan Hospital
Ms Sandra Gosley, VTE Coordinator, RBWH Safety and Quality Unit, Royal Brisbane and Women's
Hospital
Ms Debbie Humbley, Midwife, Maternity Unit, Dalby-Jandowae Health Service
Associate Professor Rebecca Kimble, Director Obstetric Services, Royal Brisbane and Women's
Hospital
Dr Alka Kothari, Staff Specialist, Obstetrics and Gynaecology, Redcliffe Hospital
Associate Professor, Kassam, Mahomed, Staff Specialist, Obstetrics and Gynaecology, Ipswich
Hospital
Dr Bruce Maybloom, Resident Medical Officer, Queensland
Ms Jody Paxton, Coordinator, Statewide Intensive Care Network, Clinical Access and Redesign Unit,
Queensland Health
Mrs Bernice Ross, Midwife, Lactation Consultant, Private Sector
Ms Meredith Shallcross, Perinatal Information Midwife, Redcliffe Hospital
Mrs Robyn Sharpe, Team Leader Physiotherapy Women's Health, Royal Brisbane and Women's
Hospital
Dr Makarla Stead, Staff Specialist, Anaesthesiology and Perioperative Services, Royal Brisbane and
Women’s Hospital
Dr Agnes Wilson, Guideline Developer/Women’s Health Coordinator, Royal Australian and New
Zealand College of Obstetricians and Gynaecologists
Ms Latisha Ryder, Consumer Representative, Maternity Coalition
Queensland Clinical Guidelines Team

Associate Professor Rebecca Kimble, Director
Ms Jacinta Lee, Program Manager
Ms Lyndel Gray, Clinical Nurse Consultant
Dr Brent Knack, Program Officer
Ms Jeanette Tyler, Clinical Nurse Consultant
Queensland Clinical Guidelines Steering Committee
Funding
This clinical guideline was funded by Queensland Health, Health Systems Innovation Branch.

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Department of Health

Maternity and Neonatal Clinical Guideline

Venous thromboembolism (VTE) prophylaxis

Great state. Great opportunity.

Document title: Venous thromboembolism (VTE) prophylaxis in pregnancy and the

Audience: Health professionals in Queensland public and private maternity services

Review date: February 2019

Information in this guideline is current at time of publication.

© State of Queensland (Queensland Health) 2014

Refer to online version, destroy printed copies after use Page 2 of 25

Flow Chart: Antenatal assessment and management for VTE prophylaxis

Antenatal VTE assessment and management

High Risk Factors

Hospitalised + ≥ 2 risk factors

# Determine dose (standard, intermediate or therapeutic) based on individual assessment

Refer to online version, destroy printed copies after use Page 3 of 25

Flow Chart: Postnatal assessment and management for VTE prophylaxis

Postnatal VTE assessment and management

Known Risk Factors Emergency

# Determine dose (standard, intermediate or therapeutic) based on individual assessment

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When a woman consents to a recommendation about her care after a process of

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1.3 Risk and benefit of VTE prophylaxis

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1.4 Risks associated with VTE prophylaxis

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1.5 Signs and symptoms of VTE

Type Clinical presentation

1.6 Transfer of care

• Consult with, refer or transfer care to higher level services as appropriate

1.7 Clinical standards

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o Ask about VTE symptoms

2.1 High risk factors for VTE

Table 3. High risk factors for VTE

Period High risk factors

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2.2 Known risk factors for VTE

Table 4. Known risk factors

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2.3 Criteria for assessment of risk

Table 5. Criteria for assessment of risk

Risk assessment Antenatal criteria Postnatal criteria

2.4 Additional assessments

Note: High risk thrombophilia include: Homozygous Factor V Leiden mutation,

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3 Options for thromboprophylaxis

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3.1 Other pharmaceutical agents

o Pregnant women: limit the use of Fondaparinux to those with severe

• Discuss newer agents with a team experienced in their use

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4 Prophylactic management of VTE

• If anticoagulation is required peripartum a multidisciplinary team approach is essential

4.1 Specific patient group management

4.2 Antenatal prophylaxis

Table 9. Antenatal prophylaxis

Risk assessment Antenatal prophylaxis

4.3 Intrapartum prophylaxis

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4.4 Postnatal prophylaxis

• UFH may be substituted for LMWH at the obstetrician/physician’s discretion [refer to